{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T01:51:22Z","timestamp":1789091482889,"version":"build-2803163510"},"reference-count":30,"publisher":"Bioscientifica","issue":"7","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5,16]]},"abstract":"<jats:p>\n                    The age-specific development of the three constituent components of multiple endocrine neoplasia type 2 (MEN 2) is incompletely characterized for many of the &gt;30 causative rearranged during transfection (\n                    <jats:italic>RET<\/jats:italic>\n                    ) mutations, which this genetic association study aimed to specify. Included in the study were 683 carriers of heterogeneous\n                    <jats:italic>RET<\/jats:italic>\n                    germline mutations: 53 carriers with 1 highest-risk mutation (codon 918); 240 carriers with 8 different high-risk mutations (codon 634); 176 carriers with 16 different intermediate-risk mutations (codon 609, 611, 618, 620, or 630); and 214 carriers with 6 different low-risk mutations (codon 768, 790, 804, or 891).There was a strong genotype-specific development of MEN 2 constituent components, with distinct age gradients from C cell disease to node negative medullary thyroid cancer (MTC), from node negative to node positive MTC, from node positive MTC to pheochromocytoma, and from pheochromocytoma to primary hyperparathyroidism. Primary hyperparathyroidism was not observed among the 53 MEN 2B patients who carried highest-risk mutations (age range: 0.5\u201350 years), of whom no more than 12 (23%) and 3 (6%) carriers were older than age 30 years and 35 years, respectively. The age-specific development of MTC differed significantly between the four RET risk categories, whereas the age-specific development of pheochromocytoma differed significantly only between the two strongest RET risk categories. No significant differences were noted in the development of primary hyperparathyroidism. These findings delineate age-specific disease manifestation corridors for the three constituent components of MEN 2 by RET genotype. These corridors are useful for initial risk assessment and organ-specific surveillance of newly identified RET carriers going forward.\n                  <\/jats:p>","DOI":"10.1530\/erc-24-0038","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T11:02:15Z","timestamp":1715857335000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":14,"title":["Genotype-specific development of MEN 2 constituent components in 683 RET carriers"],"prefix":"10.1530","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6796-079X","authenticated-orcid":true,"given":"Andreas","family":"Machens","sequence":"first","affiliation":[{"name":"Medical Faculty, Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0281-1950","authenticated-orcid":true,"given":"Kerstin","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Medical Faculty, Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0995-667X","authenticated-orcid":true,"given":"Frank","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery, Division of Endocrine Surgery, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Brandenburg","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Metabolism, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"F\u00fchrer-Sakel","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Metabolism, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Dralle","sequence":"additional","affiliation":[{"name":"Medical Faculty, Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany"},{"name":"Department of General, Visceral and Transplantation Surgery, Division of Endocrine Surgery, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"5658","article-title":"Guidelines for diagnosis and therapy of MEN type 1 and type 2","volume":"86","author":"Brandi","year":"2001","unstructured":"Brandi MLGagel RFAngeli ABilezikian JPBeck-Peccoz PBordi CConte-Devolx BFalchetti AGheri RGLibroia A, et al.2001Guidelines for diagnosis and therapy of MEN type 1 and type 2. 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Human Mutation39860\u2013869. (https:\/\/doi.org\/10.1002\/humu.23430)"},{"key":"bib16","series-title":"European Journal of Endocrinology","first-page":"469","article-title":"Sex differences in MEN 2A penetrance and expression according to parental inheritance","volume":"186","author":"Machens","year":"2022","unstructured":"Machens ALorenz KWeber F & Dralle H2022Sex differences in MEN 2A penetrance and expression according to parental inheritance. European Journal of Endocrinology186469\u2013476. (https:\/\/doi.org\/10.1530\/EJE-21-1086)"},{"key":"bib17","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"e734","article-title":"The changing face of multiple endocrine neoplasia 2A: from symptom-based to preventative medicine","volume":"108","author":"Machens","year":"2023a","unstructured":"Machens ALorenz KBrandenburg TF\u00fchrer-Sakel DWeber F & Dralle H2023aThe changing face of multiple endocrine neoplasia 2A: from symptom-based to preventative medicine. 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